This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lactation is characterized by an inhibition of reproductive cyclicity due to a suppression of gonadotropin releasing hormone (GnRH), excessive hyperphagia and negative energy balance due to milk production. The central hypothesis of this proposal is that suppression of GnRH/LH secretion is due to suckling-induced alterations in hypothalamic neural systems that regulate food intake and energy balance. Our studies have recently established that several hypothalamic neuropeptide orexigenic systems involved in regulating food intake/energy balance (NPY, orexin, melanin concentrating hormone) make direct connections with GnRH neurons, thus providing a neuroanatomical framework by which signals denoting changes in food intake/energy balance can be directly transmitted to GnRH neurons. We have also found changes in a number of substances that reflect the negative energy balance (suppressed leptin, insulin) and are likely to be involved in the chronic hyperphagia during lactation, a condition similar to obesity. Current studies are using hypothalamic explants and electrophysiology to determine if NPY, orexin or melanin concentrating hormone have direct inhibitory effects on GnRH neurons. Studies are also restoring leptin and insulin to postlactation levels and determining the effects on hypothalamic neuropeptide feeding systems and on restoration of GnRH/LH secretion. The interaction between reproductive function and energy balance during lactation provides a physiological model for studying a number of conditions in women (undernutrition, anorexia nervosa, bulimia and exercise-induced amenorrhea) that involve a suppression of reproductive function associated with changes in energy balance. The results of the studies in the rat formed the basis of a new funded project to study control of food intake in the rhesus monkey.